This Paul B. Beeson Career Development Award in Aging application is designed to further the candidate's development as an independent investigator in patient-oriented geriatric research. The career development plan builds directly on the candidate's previous training in Medicine, Neurology, Neurophysiology, and Epidemiology. The three-year career development plan emphasizes four areas: 1) longitudinal quantitative methods and analysis, 2) translational biological research, 3) gait/mobility, and 4) bioethics. Five different learning modalities are emphasized: a) formal coursework, b) reading tutorials, c) research colloquia and seminars, d) on and off-site practical with mentors, and e) supervised research proposal. Over one-third of adults over age 65 report at least one severe disability. The disablement process describes a continuum leading from disease to impairments, to functional limitations, and ultimately disability. Clinical and biological markers of the earliest stages of this process are lacking, especially in high functioning older adults. Physical and cognitive stress tests may reveal latent mobility abnormalities in high functioning older adults with low physiological reserves. The research focus of this application is to identify latent mobility abnormalities and their biological basis in non-disabled older adults. Specifically, we will 1) Examine the role of latent mobility abnormalities in response to physical and cognitive stressors as predictors of disability. 2) Determine the relationship between latent mobility abnormalities and inflammatory biomarkers. To achieve these aims, 300 non-disabled older adults will be assessed with comprehensive qualitative and quantitative mobility assessments at 6-monthly intervals over five years. Identifying latent mobility abnormalities will allow introduction of specific interventions early in the disablement process. The career development activities in this application will enable the candidate to be an independent investigator in aging, a clinical expert in cognitive and physical disability, and a mentor for the next generation of investigators. [unreadable] [unreadable]